Cargando…

Tri-methylation of H3K79 is decreased in TGF-β1-induced epithelial-to-mesenchymal transition in lung cancer

BACKGROUND: The epithelial-to-mesenchymal transition (EMT) enables epithelial cancer cells to acquire mesenchymal features and contributes to metastasis and resistance to treatment. This process involves epigenetic reprogramming for gene expression. We explored global histone modifications during TG...

Descripción completa

Detalles Bibliográficos
Autores principales: Evanno, Emilie, Godet, Julie, Piccirilli, Nathalie, Guilhot, Joëlle, Milin, Serge, Gombert, Jean Marc, Fouchaq, Benoit, Roche, Joëlle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549304/
https://www.ncbi.nlm.nih.gov/pubmed/28804523
http://dx.doi.org/10.1186/s13148-017-0380-0
_version_ 1783255949129023488
author Evanno, Emilie
Godet, Julie
Piccirilli, Nathalie
Guilhot, Joëlle
Milin, Serge
Gombert, Jean Marc
Fouchaq, Benoit
Roche, Joëlle
author_facet Evanno, Emilie
Godet, Julie
Piccirilli, Nathalie
Guilhot, Joëlle
Milin, Serge
Gombert, Jean Marc
Fouchaq, Benoit
Roche, Joëlle
author_sort Evanno, Emilie
collection PubMed
description BACKGROUND: The epithelial-to-mesenchymal transition (EMT) enables epithelial cancer cells to acquire mesenchymal features and contributes to metastasis and resistance to treatment. This process involves epigenetic reprogramming for gene expression. We explored global histone modifications during TGF-β1-induced EMT in two non-small cell lung cancer (NSCLC) cell lines and tested different epigenetic treatment to modulate or partially reverse EMT. RESULTS: Loss of classical epithelial markers and gain of mesenchymal markers were verified in A549 and H358 cell lines during TGF-β1-induced EMT. In addition, we noticed increased expression of the axonal guidance protein semaphorin 3C (SEMA3C) and PD-L1 (programmed death-ligand 1) involved in the inhibition of the immune system, suggesting that both SEMA3C and PD-L1 could be the new markers of TGF-β1-induced EMT. H3K79me3 and H2BK120me1 were decreased in A549 and H358 cell lines after a 48-h TGF-β1 treatment, as well as H2BK120ac in A549 cells. However, decreased H3K79me3 was not associated with expression of the histone methyltransferase DOT1L. Furthermore, H3K79me3 was decreased in tumors compared in normal tissues and not associated with cell proliferation. Associations of histone deacetylase inhibitor (SAHA) with DOT1L inhibitors (EPZ5676 or SGC0946) or BET bromodomain inhibitor (PFI-1) were efficient to partially reverse TGF-β1 effects by decreasing expression of PD-L1, SEMA3C, and its receptor neuropilin-2 (NRP2) and by increasing epithelial markers such as E-cadherin. CONCLUSION: Histone methylation was modified during EMT, and combination of epigenetic compounds with conventional or targeted chemotherapy might contribute to reduce metastasis and to enhance clinical responses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-017-0380-0) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-5549304
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-55493042017-08-11 Tri-methylation of H3K79 is decreased in TGF-β1-induced epithelial-to-mesenchymal transition in lung cancer Evanno, Emilie Godet, Julie Piccirilli, Nathalie Guilhot, Joëlle Milin, Serge Gombert, Jean Marc Fouchaq, Benoit Roche, Joëlle Clin Epigenetics Research BACKGROUND: The epithelial-to-mesenchymal transition (EMT) enables epithelial cancer cells to acquire mesenchymal features and contributes to metastasis and resistance to treatment. This process involves epigenetic reprogramming for gene expression. We explored global histone modifications during TGF-β1-induced EMT in two non-small cell lung cancer (NSCLC) cell lines and tested different epigenetic treatment to modulate or partially reverse EMT. RESULTS: Loss of classical epithelial markers and gain of mesenchymal markers were verified in A549 and H358 cell lines during TGF-β1-induced EMT. In addition, we noticed increased expression of the axonal guidance protein semaphorin 3C (SEMA3C) and PD-L1 (programmed death-ligand 1) involved in the inhibition of the immune system, suggesting that both SEMA3C and PD-L1 could be the new markers of TGF-β1-induced EMT. H3K79me3 and H2BK120me1 were decreased in A549 and H358 cell lines after a 48-h TGF-β1 treatment, as well as H2BK120ac in A549 cells. However, decreased H3K79me3 was not associated with expression of the histone methyltransferase DOT1L. Furthermore, H3K79me3 was decreased in tumors compared in normal tissues and not associated with cell proliferation. Associations of histone deacetylase inhibitor (SAHA) with DOT1L inhibitors (EPZ5676 or SGC0946) or BET bromodomain inhibitor (PFI-1) were efficient to partially reverse TGF-β1 effects by decreasing expression of PD-L1, SEMA3C, and its receptor neuropilin-2 (NRP2) and by increasing epithelial markers such as E-cadherin. CONCLUSION: Histone methylation was modified during EMT, and combination of epigenetic compounds with conventional or targeted chemotherapy might contribute to reduce metastasis and to enhance clinical responses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-017-0380-0) contains supplementary material, which is available to authorized users. BioMed Central 2017-08-08 /pmc/articles/PMC5549304/ /pubmed/28804523 http://dx.doi.org/10.1186/s13148-017-0380-0 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Evanno, Emilie
Godet, Julie
Piccirilli, Nathalie
Guilhot, Joëlle
Milin, Serge
Gombert, Jean Marc
Fouchaq, Benoit
Roche, Joëlle
Tri-methylation of H3K79 is decreased in TGF-β1-induced epithelial-to-mesenchymal transition in lung cancer
title Tri-methylation of H3K79 is decreased in TGF-β1-induced epithelial-to-mesenchymal transition in lung cancer
title_full Tri-methylation of H3K79 is decreased in TGF-β1-induced epithelial-to-mesenchymal transition in lung cancer
title_fullStr Tri-methylation of H3K79 is decreased in TGF-β1-induced epithelial-to-mesenchymal transition in lung cancer
title_full_unstemmed Tri-methylation of H3K79 is decreased in TGF-β1-induced epithelial-to-mesenchymal transition in lung cancer
title_short Tri-methylation of H3K79 is decreased in TGF-β1-induced epithelial-to-mesenchymal transition in lung cancer
title_sort tri-methylation of h3k79 is decreased in tgf-β1-induced epithelial-to-mesenchymal transition in lung cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549304/
https://www.ncbi.nlm.nih.gov/pubmed/28804523
http://dx.doi.org/10.1186/s13148-017-0380-0
work_keys_str_mv AT evannoemilie trimethylationofh3k79isdecreasedintgfb1inducedepithelialtomesenchymaltransitioninlungcancer
AT godetjulie trimethylationofh3k79isdecreasedintgfb1inducedepithelialtomesenchymaltransitioninlungcancer
AT piccirillinathalie trimethylationofh3k79isdecreasedintgfb1inducedepithelialtomesenchymaltransitioninlungcancer
AT guilhotjoelle trimethylationofh3k79isdecreasedintgfb1inducedepithelialtomesenchymaltransitioninlungcancer
AT milinserge trimethylationofh3k79isdecreasedintgfb1inducedepithelialtomesenchymaltransitioninlungcancer
AT gombertjeanmarc trimethylationofh3k79isdecreasedintgfb1inducedepithelialtomesenchymaltransitioninlungcancer
AT fouchaqbenoit trimethylationofh3k79isdecreasedintgfb1inducedepithelialtomesenchymaltransitioninlungcancer
AT rochejoelle trimethylationofh3k79isdecreasedintgfb1inducedepithelialtomesenchymaltransitioninlungcancer